Tuesday, May 31, 2011

Acetyl -L Carnitine (ALC)

What is it?

Acetyl-L Carnitine is an amino acid that occurs naturally in the body and is also found in milk and red meat, in particular mutton (older, mature sheep)

It is involved in the transport of fats to the mitochondria (energy producing cell structures of the cells). It also protects nerves from stress and heals damaged nerves caused by injury. In January 2002 a team of researchers showed that Acetyl -L Carnitine combined with Alpha Lipoic Acid, a fatty acid, could delay the ageing process by increasing energy (see below). Acetyl -L Carnitine was found to nourish brain cells, protect from free radicals and stress, increase blood flow, reduce depression, improve cognitive abilities and increase memory in the elderly. (We can consider that what is good for those who are aging, are also good for those with DS because they have accelerated aging.) It is indicated in the treatment of Alzheimer, AIDS, depression, fibromyalgia, heart disease, memory loss, multiple sclerosis and stress.

Acetylcarnitine and carnitine play important roles in the human body. These nutrients shuttle acetyl groups and fatty acids into mitochondria for energy production. Without carnitine, fatty acids cannot easily enter into mitochondria. The acetyl group is used to form acetyl-CoA, the most important intermediary in the generation of energy from amino acids, fats, and carbohydrates. Therefore it serves as an energy reservoir of acetyl groups and both nutrients help improve energy production. The acetyl group is also used to make the important brain chemical acetylcholine. Some studies suggest that perhaps acetyl l-carnitine can even act as a neurotransmitter itself. This nutrient is sometimes abbreviated as ALC or ALCAR.
Acetyl-L-carnitine, also known as ALCAR, is a well-researched nutritional supplement. It is synthesized to provide a more bioavailable form of L-carnitine, which is a derivative of the amino acid lysine. L-carnitine is made naturally in the body by the liver and kidneys, and then transported to other tissues such as the brain and heart. Like L-carnitine, acetyl-L-carnitine functions as an antioxidant and promotes the production of glutathione, a free radical scavenger, in cells.



Overview of benefits for those with Down syndrome
(See below for details on each.)
ADHD  In a study done by Dr. Giovanni Neri from Universita Cattolica in Rome, he saw that with ACL, there was a more effective reduction of hyperactivity and improvement of social behavior. 
Alzheimer's disease May be helpful in those with Alzheimer's disease since it protects against amyloid-beta neurotoxicity 
Anti-aging and longevity with alpha lipoic acid Scientists at the University of California, Berkeley, CA rejuvenated aging rats by giving them a combination of alpha lipoic acid and acetylcarnitine. 
Memory Studies in aging rats shows acetyl-l-carnitine increases cholinergic synaptic transmission and consequently enhances learning capacity. The memory of aging rats is rejuvenated by giving them a combination of acetylcarnitine and lipoic acid. 
Improved Visual Functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005. 
Why is it necessary?

Because L-carnitine is involved in cellular metabolism, acetyl-L-carnitine can help increase energy production in the mitochondria, the "power plants" of all cells, and thereby may generally boost physical and mental energy. As a dietary supplement, acetyl-L-carnitine is often used to help improve memory, and has been studied as a possible adjunct treatment for Alzheimer's disease. Acetyl-L-carnitine may also help address symptoms of depression, and may be useful in the treatment of Parkinson's disease, stroke, and Peyronie's disease. In addition, daily supplementation with acetyl-L-carnitine may have a protective effect on the central nervous system and may benefit the heart. There is also some evidence that acetyl-L-carnitine can enhance visual memory and attention in people with Down Syndrome (see below), and clinical data indicates that it also may slow age-related mental decline that is not associated with Alzheimer's.


For products I use for Jett, see the DS Day to Day Store


I give Jett (began when he weighed about 22 lbs, now he's at 26.4 lbs) two servings of about 500 mg each serving w/food. Once in am and once in the afternoon. I see that this dose is high. I haven't seen any hyperactivity, though. He still takes his nap fine and falls asleep at night.

Why Acetyl-L-Carnitine for the Down Syndrome population?

Clin Ter. 1994 Feb;144(2):123-7.

[Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome].

[Article in Italian]

Source

Cattedra di Neurofisiopatologia, II Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli.

Abstract

Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non-Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.

Dosage and frequency of use


The typical daily dosage for long term use is 100 to 300 mg once a day, preferably in the early part of the day.  Higher amounts, such as 500 to 1000 mg, can be taken for short periods. Most people begin to notice the effect from after an hour or two, and the mental enhancement can last a few hours or all day depending on the dosage. There are many different dosages available over the counter ranging from 100 mg to 500 mg or more. 
Dr. Weil recommends 500 to 1,500 mg per day for an adult.

I give Jett (weighs about 22 lbs) two servings of about 500 mg each serving w/food. Once in am and once in the afternoon. I see that this dose is high. I haven't seen any hyperactivity, though. He still takes his nap fine and falls asleep at night.

Dosing Notes

Acetyl-L-carnitine is a powerful anti-aging nutrient that is beneficial for mild mental impairment; practitioners recommend 1,000 to 2,000 mg a day for up to ninety days.

Power Aging by Gary Null, page 192 

Results of this double-blind, placebo-controlled study found that treatment with 2 g of acetyl-L-carnitine per day for 24 weeks had beneficial short-term memory effects on patients with Alzheimer-type dementia.
The Clinician's Handbook of Natural Healing by Gary Null PhD, page 711
Several major studies have shown that daily supplementation with ALC significantly slows the progression of Alzheimer's disease, resulting in less deterioration in memory, attention and language, and spatial abilities.
Prescription for Nutritional Healing by Phyllis a Balch CNC and James F Balch MD, page 46
Results of this double-blind, placebo-controlled study showed that the administration of 2g per day of acetyl-L-carnitine for three months led to significant improvements in elderly patients suffering from mental impairment.
The Clinician's Handbook of Natural Healing by Gary Null PhD, page 854
Elderly patients receiving acetyl-L-carnitine at doses of 1,000 to 2,000 mg a day for up to ninety days found relief from mild mental impairments such as slow memory.
Power Aging by Gary Null, page 93
Results of this double-blind, placebo-controlled study indicated that the
administration of 1500 mg per day of acetyl-L-carnitine to elderly patients with mild mental impairments proved to be beneficial against cognitive and emotional-affective mental impairment.
The Clinician's Handbook of Natural Healing by Gary Null PhD, page 706


Side effects
ALC is believed to be safe and is available without prescription at health food stores. Side effects of overstimulation, restlessness, and nausea may occur at dosages greater than 500 mg. Even higher doses may cause insomnia. If you happen to feel nausea, next time just take the acetyl l-carnitine with food or take a lesser dose. A few people may notice mild headaches.
Side effects can include mild gastrointestinal symptoms, such as nausea, vomiting, and abdominal cramps, as well as headache; an increase in agitation or restlessness; and an increase in seizure frequency in persons with seizure disorder. Persons with Alzheimer's disease may exhibit psychiatric disturbances, such as depression and confusion, but it is uncertain whether these effects are due to acetyl-L-carnitine or the disease itself. Some evidence suggests acetyl-L-carnitine may interfere with thyroid metabolism, so watch for symptoms. I haven't seen issues worsen on ACL in Jett.

Can Cognitive Deterioration Associated with Down Syndrome be Reduced?
By R. Thiel, Ph.D., Naturopath and S.W. Fowkes, B.A.

At least in eyes, it appears that acetyl-L-carnitine may have antiglycation abilities (55). Hendlor and Rorvik report, “”Acetyl-L-carnitine has recently demonstrated some efficacy as a possible neuroprotective agent for strokes, Alzheimer’s disease, Down’s syndrome and for the management of various neuropathies…recent studies show beneficial effects in Alzheimer’s disease. Younger patients seem to benefit most” (55). However, some few with seizure disorders have reported increases in seizure frequency or severity on acetyl-L-carnitine (54). As the DS population is much more inclined towards seizure disorders than the general public (56), caution would seem to be advisable regarding using acetyl-L-carnitine to attempt to prevent glycation. 
54. Hendlor SS, Rorvik D, eds. PDR for Nutritional Supplements. Medical Economics. Montvale (NJ) 2001
55. Swamy-Mruthinti S, Carter AL. Acetyl- L -carnitine decreases glycation of lens proteins: in vitro studies. Exp Eye Res. 1999;69(1):109-115
56. Thiel R, Fowkes SW. Down syndrome and epilepsy: A nutritional connection? Med Hypo. 2004; 62(1):35-44 

Research
- Ageing: - Liu J, Head E, Gharib AM, Yuan W. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):2356- "These results suggest that feeding ALCAR .. (acetyl-l-carnitine) ..and LA (R-alpha-lipoic acid) to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function."
- Hagen TM, Liu J, Lykkesfeldt J, Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 2002 Feb 19;99(4):1870-5 "Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone."
- Ando S, Tadenuma T, Tanaka Y, Fukui F Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res 2001 Oct 15;66(2):266-71
- Sorbi S, Forleo P, Fani C, Piacentini S. Double-blind, crossover, placebo-controlled clinical trial with L-acetylcarnitine in patients with degenerative cerebellar ataxia. Clin Neuropharmacol 2000 Mar-Apr;23(2):114-8 "After the trial, we observed a statistically significant improvement of some symptoms and a slow progression of the disease in both groups of patients."
- Acetyl-L-carnitine. Altern Med Rev 1999 Dec;4(6):438-41 " Studies have shown that ALC may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, diabetic neuropathies, ischemia and reperfusion of the brain, and cognitive impairment of alcoholism."

Benefit Details

ADHD benefit

L-acetylcarnitine may help with attention deficit hyperactivity disorder in children with the genetic disorder known as fragile X syndrome which results from an inherited genetic defect on the X chromosome. It is associated with  mental retardation and may also cause autism and ADHD, Dr. Giovanni Neri from Universita Cattolica in Rome studied boys between 6 and 13 years old for a period one year. Twenty four received l-acetylcarnitine and 27 received placebo. There was a more effective reduction of hyperactivity and improvement of social behavior. American Journal of Medical Genetics 2008.


Alzheimer's disease


May be helpful in those with Alzheimer's disease since It protects against amyloid-beta neurotoxicity.

Effects of acetylcarnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.
Curr Med Res Opin. 2003.
An evaluatation was made of the effect of 2 grams /day orally for 3 months in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of acetylcarnitine.


Anti-aging and longevity with alpha lipoic acid

Scientists at the University of California, Berkeley, CA rejuvenated aging rats by giving them a combination of alpha lipoic acid and acetylcarnitine. Lead researcher Dr Bruce Ames, said the results were astonishing: "With the two supplements together, these old rats got up and did the Macarena. The brain looks better, they are full of energy - everything we looked at looks more like a young animal." The animals' memories were also significantly  improved. The two chemicals in combination have a positive impact on  mini-organs within the body's cells called mitochondria and were able to mop up free radicals. Mitochondria generate energy within the cells and  their deterioration  is an important cause of aging.
   It is difficult to predict whether this combination is effective in humans, and if so, how to determine the ideal dose combination. In the meantime, those who wish to supplement prudently with small amounts may consider taking  about 5 to 10 mg of lipoic acid, and 30 to 100 mg of acetyl-l-carnitine. Since these nutrients are not often available over the counter in these small doses, you may need to open the capsules and take a portion. 


Chronic fatigue syndrome

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome.
Psychosom Med. 2004.
We compared 2 grams a day acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 chronic fatigue syndrome patients during 24 weeks. Acetylcarnitine significantly improved mental fatigue and propionylcarnitine improved general fatigue.


Depression and low mood

ALCAR may benefit geriatric patients with mild depression.


Diabetic neuropathy

Acetyl-L-carnitine in the treatment of diabetic neuropathy. A long-term, randomized, double-blind, placebo-controlled study.
Drugs R D. 2002.
A group of 333 patients with diabetic neuropathy were enrolled. Acetylcarnitine (or placebo) was given orally at a dosage of 2000 mg/day. This natural medicine was effective and well tolerated in improving neurophysiological parameters and in reducing pain over a 1-year period.

Acetyl L Carnitine Improves Pain, Nerve Regeneration, and Vibratory Perception in Patients With Chronic Diabetic Neuropathy: An analysis of two randomized placebo-controlled trials.
Diabetes Care. 2005.
We evaluated frozen databases from two 52-week randomized placebo-controlled clinical diabetic neuropathy trials testing two doses of acetyl-l-carnitine : 500 and 1,000 mg/day three times a day. Data showed significant improvements in sural nerve fiber numbers and regenerating nerve fiber clusters. Nerve conduction velocities and amplitudes did not improve, whereas vibration perception improved in both studies. Pain as the most bothersome symptom showed significant improvement in one study and in the combined cohort taking 1,000 mg.


Hypertension and insulin resistance

Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy.
Hypertension. 2009.
We prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate in nondiabetic subjects at increased cardiovascular risk. It safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia.


Memory

Studies in aging rats shows chronic administration of acetyl-l-carnitine increases cholinergic synaptic transmission and consequently enhances learning capacity. The memory of aging rats is rejuvenated by giving them a combination of acetylcarnitine and lipoic acid.


Neuropathy

A pilot study on the effect of acetylcarnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.
Tumori. 2005.
Twenty-seven patients with paclitaxel and/or cisplatin-induced neuropathy received at least one cisplatin or one paclitaxel based regimen, or a combination of both. Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die i.v. infusion over 1-2 hours for at least 10 days and it seemed to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy.


Peyronie's disease

ALCAR is more effective than tamoxifen in the therapy of acute and early chronic Peyronie's disease.


Vision research study

Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.
Ophthalmologica. 2005.
The aim of this randomized, double-blind, placebo-controlled clinical trial was to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus alterations in early age-related macular degeneration. Findings suggest that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early age-related macular degeneration.


Weight loss

Some people notice ALC reduces appetite but I have not seen formal studies using this supplement as an effective weight loss pill.


What you may notice after taking a supplementThose who take carnitine pills notice an increase in physical energy, but not as much mental energy. Acetyl l-carnitine has a more immediate and noticeable mental effect than carnitine because it crosses into the brain much better and quicker. The mind boosting effect of ALC is often noticed within a few hours, or even within an hour. Most people report feeling mentally sharper, having more mental stamina, having more focus and being more alert. Some find a mild mood enhancement. 

Sources


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